| abstract |
Novel cyclic CRF antagonist peptides have the amino acid sequence: (cyclo 30-33)Y-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-R30-Ala-R32-R33-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2, wherein Y is Ac, H, Ac-Thr or H-Thr; R30 is Glu or Cys; R32 is His or preferably a basic and/or aromatic D-amino acid such as D-His or D-Arg; R33 is Lys, Orn or Cys. The N-terminus may be extended by Leu or Asp-Leu. CML may be substituted for Leu27, and D-Tyr may be substituted for D-Phe to facilitate labelling. Lys may be substituted for Arg23, and its side chain connected by a lactam bridge to Glu20 to form a bicyclic peptide. Disclosed CRF antagonists include: (cyclo 30-33)[D-Phe?12, Nle21,38, Glu30, Lys33¿]r/hCRF(12-41); cyclo 30-33)[Ac-Thr?11, D-Phe12, Nle21,38, Glu30, Lys33¿]r/hCRF(11-41); (cyclo 30-33)[D-Phe?12, Nle21,38, Cys30-33¿]r/hCRF(12-41); (bicyclo 20-23, 30-33)[D-Phe?12, Nle21,38, Lys23,33, GLu30¿]-r/hCRF(12-41); (cyclo 30-33)[D-Phe?12, Nle21,38, Glu30, D-His32, Lys33¿]r/hCRF(12-41); (cyclo 30-33)[D-Phe?12, Nle21,38, CML27, Glu30, D-His32, Lys33¿]r/hCRF(12-41) and (cyclo 30-33)[D-Phe?12, Nle21,38, Glu30, D-Arg32, Lys33¿]r/hCRF(12-41). Labelled antagonists such as (cyclo 30-33)[I?125D-Tyr12, Nle21,38, Glu30, D-His32, Lys33¿]r/hCRF(12-41) are useful in drug screening assays. |